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Nerve Trauma and Spinal Cord Injury

A. Parallel fibers seen with transmitted light. B. Neurites, stained for neurofilament in fluorescent light, extend from the large DRG on the right, labeled with a G, and continue going leftward until they contact fibers, then turn to follow them in the up and down direction. Note that all neurites on the left side of the photograph travel vertically.

Physical damage to nerves is a leading cause of disability. Nerves are essential for coordination and movement of the limbs. When a patient suffers a traumatic injury, such as a car accident, fall, or surgical error, the loss of limb use can be devastating to the quality of life. Cut nerves tend to degenerate because they have lost contact with the muscle that they controlled. Yet, the nerve possesses some ability to re-grow, and to date physical therapy and waiting are the only treatments. PNR&D investigators are working on improving recovery following nerve and spinal cord trauma.

C. A small DRG on glass adjacent to a fiber extends neurites radially in all directions on the glass (right) while those on the side of the fiber bundle (left) follow fibers close to the ganglion. D. After five days, neurites migrated at least one half the distance of the cover slip (11 mm), but stop at the band-aid holding down the fibers. They do not continue migrating on to the glass or band-aid, both of which are also coated with collagen.

First, in complimentary studies to the neurodegenerative diseases ALS and diabetes complications, PNR&D investigators are exploring therapeutic compounds that prevent or decrease neuronal degeneration or promote regeneration.

Second, PNR&D investigators are examining the potential to encourage nerves to re-grow by providing them with a framework to direct the growth process. Drugs that promote nerve growth generally produce random nerve sprouts that would produce a hit-or-miss kind of recovery. PNR&D investigators, therefore, are making a new kind of nerve support that will allow damaged nerves to re-connect correctly. These artificial structures are produced using fibers that are narrower than a human hair. The therapeutic compounds that promote neuron survival can be embedded in the fibers to increase regeneration.

Top: Aligned nanofibers taken on scanning electron microscope. Middle: Spinal cord motor neuron grown on nanofiber scaffold for 4 days.  The neuron develops normally, having an axon (arrow) and three dendrites, one to the right (arrowhead) and two to the left of the large cell body with its blue nucleus. Bottom:  Sensory neurons (in green) and their supporting Schwann cells (red) grown on nanofibers.  Note how all the cells grow oriented parallel to the nanofibers which span from the left to right.

Recently, PNR&D investigators have developed new methods of producing these nanofibers that are completely non-toxic and can be tested with motor and sensory nerve cells.  In this way, the effects that fibers have on nerve cell development can be studied.  We have recently found that these nanofibers accelerate the development of nerve cells so that they can form connections with each other more rapidly.  The alignment of nanofibers allows more rapid growth of nerve cells, so that nerve repair can happen more rapidly. 

PNR&D investigators have also implanted these nanofiber scaffolds into nerve injuries in mammals to test their effectiveness in promoting nerve injury.  More work remains to be done by incorporating different growth factors into them and coating them with proteins that promote nerve growth.  These scaffolds may also be useful for spinal cord injury as well as guiding new nerve growth to artificial prosthetic limbs.

 

Current research projects by PNR&D investigators:

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